SGX523 / Eli Lilly - LARVOL DELTA

The role of SLC22A4 in Acute Myeloid Leukaemia. (PubMed, Mediterr J Hematol Infect Dis) - "Drug-sensitivity analysis showed positive correlations with cyclobenzaprine, hydrochloride, SGX-523, and simvastatin, and negative correlations with fluorouracil, abexinostat, EMD-534085, hypothemycin, tamoxifen, and sunitinib. SLC22A4 may be useful as a potent molecular-targeted agent in AML."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Thrombin receptor PAR4 cross-activates the tyrosine kinase c-met in atrial cardiomyocytes. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "The c-met inhibitor SGX-523 abrogated the effects of PAR4-AP on CaMKII/AKT/mTOR phosphorylation but did not affect PAR4-stimulated IL-1β production...Transactivated c-met contributes partially to PAR4-mediated signaling, but NLRP3 inflammasome activation appears to be largely independent of c-met. Abundance of PAR4 and activated c-met increases with obesity, providing therapeutic targets for management of adiposity-driven AF."

Journal • Genetic Disorders • Obesity • Oncology • ACTA2 • AMPK • IL1B • MET • MPO • NLRP3

Construction of a Liver Cancer Prognostic Model Based on Interferon-Gamma-Related Genes for Revealing the Immune Landscape. (PubMed, J Environ Pathol Toxicol Oncol) - "Drugs that had high correlations with the feature genes included SPANXB1: PF-04217903, SGX-523, MMP1: PF-04217903, DUSP13: Imatinib, TFF1: KHK-Indazole, and Fulvestrant. It was found that L-group patients were more suitable for immunotherapy. This study provided valuable information on the prognosis of liver cancer."

IO biomarker • Journal • Gastrointestinal Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • DUSP1 • IFNG • MMP1 • TFF1

SGX523 causes renal toxicity through aldehyde oxidase-mediated less-soluble metabolite formation in chimeric mice with humanized livers. (PubMed, Toxicol Lett) - "Additionally, this activity in the liver cytosolic fraction from humanized-liver mice was inhibited by the AOX inhibitors raloxifene and hydralazine. The accumulation of amorphous material in the tubules and infiltration of inflammatory cells around tubules were observed in the kidneys of humanized-liver mice after repeated oral SGX523 administration. These findings demonstrate that humanized-liver mice are useful for understanding the metabolism and toxicity of SGX523."

Journal • Preclinical • Renal Disease • MET

Autocrine EGF and TGF-α promote primary and acquired resistance to ALK/c-Met kinase inhibitors in non-small-cell lung cancer. (PubMed, Pharmacol Res Perspect) - "Clinically, NSCLC patients with high expression of EGF and TGF-α developed primary resistance to crizotinib. Furthermore, combined treatment with gefitinib circumvented EGF- and TGF-α-mediated primary and acquired resistance to TAE684/SGX-523. Taken together, these results suggested increased autocrine EGF and TGF-α conferred primary and acquired resistance to ALK/c-Met kinase inhibitors in NSCLC."

Journal • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET • TGFA

Functional proteomics of patient derived head and neck squamous cell carcinoma cells reveal novel applications of trametinib. (PubMed, Cancer Biol Ther) - "These yielded several candidates, including axtinib, GDC-0032, GSK-690693, and SGX-523. The combination regimen of trametinib and AXL/MET/VEGFR inhibitor glesatinib showed initial efficacy both in vitro and in vivo (92% reduction in tumor volume)...Furthermore, resistant cell lines showed a compensatory mechanism via increases in MAPK and non-MAPK pathway proteins that may represent targets for future combination regimens. Intrinsic-targeted options have potential to address paucity of medical treatment options for HNSCC cancer patients, enhance response to extrinsic targeted agents, and/or reduce morbidity as neoadjuvant to surgical treatments."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • AXL

CircFAM53B promotes the proliferation and metastasis of glioma through activating the c-MET/PI3K/AKT pathway via sponging miR-532-3p. (PubMed, Cell Cycle) - "Moreover, the treatment of the c-MET inhibitor SGX523, the PI3K inhibitor LY294002, and the Akt inhibitor MK-2206 reduced circFAM53B-mediated oncogenic effects. Conclusively, circFAM53B aggravated glioma progression by up-regulating the c-MET/PI3K/AKT pathway and down-regulating miR-532-3p. Thus, the circFAM53B/miR-532-3p/c-MET/PI3K/AKT axis is a potential treatment target for glioma."

Journal • Brain Cancer • Glioma • Oncology • Solid Tumor • BAX • BCL2 • MET

Peroxisome Proliferator-Activated Receptor gamma negatively regulates liver regeneration after partial hepatectomy via the HGF/c-Met/ERK1/2 pathways. (PubMed, Sci Rep) - "Before surgery, mice were either treated with the PPARγ agonist rosiglitazone, the PPARγ antagonist GW9662 alone, or with the c-met inhibitor SGX523. Our data support the concept that PPARγ abrogates liver growth and hepatocellular proliferation by inhibition of the HGF/c-Met/ERK1/2 pathways. These pathways may represent potential targets in response to liver disease and could impact on the development of molecular therapies."

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